1. Pain Management In The Hospitalized Patient Presented By R2 顏郁軒 92/09/16

2. 出處 Medical Clinics of North America Volume 86 Number 4 July 2002

3. Pain introduction Pharmacokinetic considerations Drug introduction ( opioids, NSAIDs, adjuvant drug ) The World Health Organization three- step analgesic ladder

4. Pain Introduction (1) Nociceptors are free nerve endings, innervated by A-delta and C nerve fibers, which reside among mast cells and countless blood vessels Neurotransmitters : substance P, glutamate, prostaglandins and leukotrienes spinothalamic and spinoreticular tracts

5. Pain Introduction (2) Hypothalamus, pons and somatosensory cortex : stimulation of these areas causes analgesia Three endogenous systems involved in the inhibitory pathways for pain: (1) the opioid system, (2) the noradrenergic system, and (3) the serotonergic system

6. Pain Introduction (3) Types of pain : somatic pain, visceral pain, neuropathic pain Evaluation and measurement of pain Pain should be treated as a vital sign

7. Pharmacokinetic consideration (1) Pharmacokinetics is the process of drug absorption, distribution, and elimination Drug concentration: high concentrations of a drug tend to be absorbed more rapidly than low concentrations. Increased circulation: increased circulation at the site of absorption can enhance absorption (eg, heat and massage). Area exposed to the drug: absorption occurs more rapidly over larger surface areas. Drug solubility: drugs in oily solutions are less readily absorbed than those delivered in aqueous solution. Route of administration: oral administration of drugs is the most common and often safest, most convenient and cost efficient method of drug delivery.

8. Pharmacokinetic consideration (2) Drug distribution Drug binding Biotransformation Elimination : Drugs can be excreted in active or inactive forms in numerous ways

9. Opioids (1) Drugs are defined as “ opioids ” if they bind to the opioid receptor and elicit agonist activity anterior pituitary gland : endogenous opioids such as endorphins, dysmorphins, and enkephalins Opioid receptors are found not only in the CNS, but also in musculoskeletal structures, in visceral and vascular smooth muscle, and at the terminals of sympathetic and sensory peripheral neurons

10. Opioids (2) Side Effect : respiratory, cardiac, GI, CNS, Muscle, GU Dose-dependent effect : respiratory, CNS Drug introduction : Morphine, Codeine, Fentanyl, Meperidine, Propoxyphene ( Depain ),

11. Morphine (1) Morphine, unlike some of the other opioids, causes histamine release, which can cause vasodilation and potential hypotension renally excreted Oral forms of morphine : immediate release or sustained release preparations

12. Morphine (2) Table Equivalent narcotic dosing chart NarcoticIM/IV (mg)PO (mg)Duration (hrs) Codeine12020094–6 Fentanyl.1–91–2 Hydromorphone1.57.594–5 Meperidine7530092–4 Methadone102094–6 Morphine1030–6093–7 Oxycodone–15–3094–6 Oxymorphone1–93–6 Propoxyphene–13094–6

13. Morphine (3) Effect of oral morphine : parenteral morphine 約 1:3 traditional short-acting oral morphine and extended release oral morphine converted ; short-acting morphine can be given for any breakthrough pain MST : The tablets should be swallowed whole and not chewed, crushed, or dissolved

14. Codeine low analgesic potency, more frequently used as an antitussive has a “ ceiling effect

15. Fentanyl (1) 100 times more potent than morphine highly lipid-soluble  more than 80% of an injected dose is redistributed from the plasma in less than five minutes metabolized in the liver Transdermal fentanyl is usually used to provide continuous analgesia rather than management of breakthrough pain

16. Fentanyl (2) When using transdermal fentanyl, it is important to always provide short-acting opioids for breakthrough pain temperature-dependent increase in fentanyl released from the transdermal system

17. Meperidine only one-tenth as potent as morphine 90% of meperidine is metabolized in the liver to normeperidine ( half-life up to 40 hours )

18. Propoxyphene ( Depain ) it has a metabolite with a long half-life (norpropoxyphene) and is associated with neuroexcitation

19. Acetaminophen With the addition of acetaminophen, opioid requirements can be reduced up to 30% Hepatoxicity can occur with acute intoxication with more than 15 g/day 500 ~ 1000 mg q3h ~ q6h In liver disease : < 2 gm/d In healthy : < 4 gm/d

20. Nonsteroidal anti-inflammatory drugs (1) Traditional NSAIDs are effective in the treatment of mild to moderate pain, but their use is limited by potentially serious adverse effects ketorolac : indicated only in the management of moderately severe acute pain that requires opioid level analgesics ; no more than 5 days

21. Nonsteroidal anti-inflammatory drugs (2) COX-2 selective inhibitors [celecoxib (Celebrex), rofecoxib (Vioxx) and valdecoxib (Bextra)] 200-fold to 300-fold selectivity for inhibition of COX-2 over COX-1

22. Tramadol centrally acting synthetic analgesic whose mode of action is not completely understood minimal sedation or respiratory depression For moderate to moderately severe pain

23. Antiepileptic drugs Antiepileptic drugs have been used for many years in the treatment of neuropathic pain phenytoin, carbamazepine, and valproic acid The newer agents, gabapentin appears to be the most effective and well tolerated

24. Phenytoin postherpetic neuralgia side effects include gingival hyperplasia and even peripheral neuropathy Dosage : 100 mg TID Require blood test if long term used

25. Carbamazepine ( Tegretol ) for trigeminal neuralgia, diabetic neuropathy, and pain syndromes associated with multiple sclerosis hematological side effects and chronic use also requires regular blood tests Dosage : 100 mg/d up to 1200 mg/d

26. Gabapentin (Neurontin) postherpetic neuralgia and diabetic neuropathy Initial dosage : 300 mg TID, may up to 3.6 gm/d

27. Antidepressants Antidepressants are effective agents in the treatment of neuropathic pain serious side effects, include anticholinergic effects including dry mouth, confusion, and urinary retention Imipramine ( Tofranil ) : 50~150 mg/d

28. The World Health Organization three-step analgesic ladder

29. Each step of the WHO Analgesic Ladder encourages the use of adjuvant analgesic agents Adherence to this guideline with appropriate dosing of drugs can provide adequate pain relief in 70% to 90% of patients

30. Concerns surrounding the use of opioids fewer than 1 in 1000 patients using opioids for pain would be expected to develop an addiction Addiction, Physical dependence, Tolerance Addiction is not a predictable drug effect. Physical dependence and tolerance are predictable

31. Conclusion Pain is unnecessary. Effective tools are available to help doctors evaluate pain in their patients. Unrelieved pain should be treated just like any other vital sign: with aggressive measures. Effective therapies are available to treat pain. Use guidelines to develop a rational plan to relieve pain. Side effects are manageable. Anticipate side effects and treat aggressively. Addiction rarely occurs. Trust your patient when they report pain. Tolerance and physical dependence can occur. Plan and you will succeed. Take the initiative and focus on relieving pain at your hospital. Your patients depend on it.

32. Thanks for Your Attention !!!